Death or Neurodevelopmental Impairment at 18 to 22 Months Corrected Age in a Randomized Trial of Early Dexamethasone to Prevent Death or Chronic Lung Disease in Extremely Low Birth Weight Infants Ann R. Stark, Waldemar A. Carlo, Betty R. Vohr, Lu Ann Papile, Shampa Saha, Charles R. Bauer, William Oh, Seetha Shankaran, Jon E. Tyson, Linda L. Wright, W. Kenneth Poole, Abhik Das, Barbara J. Stoll, Avroy A. Fanaroff, Sheldon B. Korones, Richard A. Ehrenkranz, David K. Stevenson, Myriam Peralta-Carcelen, Deanne E. Wilson-Costello, Henrietta S. Bada, Roy J. Heyne, Yvette R. Johnson, Kimberly Gronsman Lee, Jean J. Steichen, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network et al.
To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18-22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants.
Evaluation of infants at 18-22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index and the Psychomotor Developmental Index. NDI was defined as moderate or severe cerebral palsy, Mental Developmental Index or Psychomotor Developmental Index <70, blindness, or hearing impairment.
Death or NDI at 18-22 months corrected age was similar in the dexamethasone and placebo groups (65% vs 66%, P = .99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50% vs 41%, P = .42 for weight less than 10th percentile); 49% of infants in the placebo group received treatment with corticosteroid compared with 32% in the dexamethasone group (P = .02).
The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group.
This is a multicenter randomized double masked, placebo controlled trial conducted by the NICHD Network between 1998 and 1999. Primary outcome was death or neurodevelopment impairment (NDI) at 18-22 months corrected age (CA).
The trial was stopped early because of an unanticipated and unacceptable rate of GI perforations in the dexamethasone group. In 2-by- 2 factorial design, infants were randomly assigned to 1 of 4 groups according to study medication (dexamethasone or placebo) and ventilator management (routine treatment or permissive hypercapnia). Inclusion criteria BW: 501-1000 g, treatment with mechanical ventilation within 12 hours from birth and indwelling vascular catheter.
Infants with known primary outcomes, death and NDI, were similar in both groups. Although a secondary analysis study showed the placebo group, exposed to clinical steroid treatment, tended to have worse outcomes. Authors agreed the available evidence does not support the routine use of postnatal early dexamethasone. Whether subgroups at extremely high risk for CLD would benefit from late low-dose dexamethasone needs to be further investigated.
Oscar Winners-Mendizabal, M.D.